1. Field of the Invention
This invention relates to the field of hyperprolactinemias, and prolactinomas. More specifically, this invention relates to the treatment of a subject afflicted with either condition, and the lowering of prolactin levels and/or the size of the tumor by administration of a selected family of pharmaceuticals.
2. Description of the Background
Prolactin hypersecretion, or hyperprolactinemia, may have anyone of a number of functional causes, including various neurogenic causes such as thoracic sensory nerve stimulation, stress, and psychogenic causes, various hypothalamic causes such as diffuse processes, granulomatous diseases, neoplasms, stalk section, empty sella, non-lactotropic cell pituitary tumors, and prostradiation treatment to sella, various pituitary causes such as prolactinomas and pituitary lactotropic cell hyperplasia, and various endocrine causes such as pregnancy, estrogen administration, hypothyroidism, and adrenal insufficiency. Prolactin hypersecretion may also be caused by the administration of drugs which impair dopamine secretion, such as psychotropic drugs, antihypertensive drugs, antiemetic drugs, H.sub.2 -receptor blockers, and opiates, among others.
Prolactinomas are pituitary tumors, in fact, the most common pituitary tumors, which are almost five times more common in women than in men. Some prolactinomas respond to, and may be treated with, the dopamine agonist, Bromocriptine. One-third of the patients afflicted with prolactinomas, however, do not respond to, and are therefore not treatable with, this drug. The latter are usually referred for pituitary surgery and/or, rarely, irradiation.
Somatostatin, also known as somatotropin release inhibiting factor or SRIF, is believed to exert its biological effect through a family of G-protein associated receptors provided with seven transmembrane domains. Somatostatin inhibits the secretion of growth hormone. Five subtypes of the somatostatin receptor (SSTR) have already been cloned, and named SSTR-1, SSTR-2, SSTR-3, SSTR-4, and SSTR-5. The SSTR-1, SSTR-2, and SSTR-5 receptors have been shown to be expressed by the human pituitary gland, and the SSTR-1, SSTR-2, SSTR-3 and SSTR-5 receptors by human pituitary adenomas.
A large number of somatostatin agonists have been synthesized, and shown to preferentially bind to selected subtypes of the somatostatin receptor (SSTR) (See, below). Up until now, only SSTR-2 selective somatostatin agonists were shown to inhibit prolactin secretion from normal fetal pituitary cultures.
Up to the present time, thus, it was not known which subtype(s) of the SSTR mediate(s) the regulation of prolactin production and secretion in the state of pathological hyperprolactinemia, such as that resulting, for example, from a prolactinoma.